Information on fast axonal transport in normal and diseased human nerve is virtually non-existent. We have an opportunity to fill this gap in knowledge by interfacing sophisticated microscopy, video, and computer technology with clinical neurologic medicine. We aim to: 1) Quantitate with high spacial and temporal resolution multiple variables of organelle motion in human axons; 2) Develop a large data base on the basic phenomenology of fast axonal transport in normal human motor and sensory nerves (by studying these in non-ischemic amputated human limbs); 3) Test the hypothesis that amyotrophic lateral sclerosis (ALS) is a disorder characterized by abnormal axonal transport (by studying motor nerve biopsies from ALS patients); 4) Test the hypothesis that periphral polyneuropathies of various types are characterized by an abnormality of fast axonal transport. Three technologies - interference contrast optics, video image enhancement, and computer image processing with semi-automatic organelle tracking - make it possible to detect moving organelles 30-5,000 nm in size, track their motion, and display data on distances travelled, instantaneous velocities, and accelerations in multiple graphic formats. Motion profiles of different size-range organelles moving in sensory, motor, normal and diseased axons will be compared and correlated with clinical, electromyographic, and EM ultrastructural data. Until this information on axonal transport in human nerve is established, the physiology and possible pathophysiology of this phenomenon in crippling and lethal neurologic disease cannot be fully elucidated.